Evaluation of the effects of 17beta-estradiol on the mesenteric injury induced by supraceliac aortic oclusion in male rats

Abstract

Tissue ischaemia determines a set of metabolic changes that may lead to cellular death. Although essential to prevent tissue damage, the restoration of blood flow itself may aggravate ischaemic injury, phenomenon which is entitled ischemia/reperfusion injury. Regarding aortic reconstructive surgery, the supraceliac aortic occlusion may compromise the blood flow of either the organs close to the aortic clamp or the distant ones such as the gastrointestinal tract. The mesenteric ischaemia is associated with intestinal mucosal injury and decreased intestinal barrier function with devastating consequences for patients. It is a life-threatening emergency with mortality rate ranging from 60% to 80%, moreover the survival rate has not improved substantially over the last decades, considering that its clinical presentation is nonspecific in most cases. Clinical and experimental evidence attest that sex hormones influence the course of the inflammatory lesion, emphasizing the beneficial effect of the female hormone oestrogen and the deleterious effect of the male hormone testosterone. Furthermore, the gonadal steroid 17beta-oestradiol protects the cardiovascular system from ischaemic, inflammatory and metabolic lesions. Recent data indicate that administration of 17beta-oestradiol to ovariectomised females or male rats subjected to haemorrhagic shock restores cardiac, hepatocellular, and immunological functions. There is no evidence indicating the role of this hormone on the mesenteric ischaemic injury inflicted by the aortic ischaemic event, especially with the use of a model in which the mesenteric ischaemia will be induced by the occlusion of the descending aorta via intravascular catheter, manoeuvre characterised by reduced surgical trauma. It is intended to investigate: (1) mesenteric microcirculatory changes such as perfusion, leukocyte-endothelial interactions and adhesion molecules expression, (2) plasma cytokines concentration, (3) white blood cell counts, (4) haemodynamic and blood gas variables; (5) intestinal vascular permeability and myeloperoxidase activity; (6) protein and genic expression of nitric oxide synthase isoforms and endothelin (7) plasma oestradiol levels. (AU)